1. Field of the Invention
The present invention relates to a homolog of human CD147 discovered in baboon tissue and its uses.
2. Description of the Related Art
EMMPRIN (extracellular matrix metalloproteinase inducer), also called basigin, leukocyte antigen M6, or CD147, is a member of the immunoglobulin superfamily. CD147 is a transmembrane glycoprotein, containing an extracellular Ig-like C2-type domain followed by an Ig-like V-type domain. CD147 is present on the surface of tumor cells and stimulates the production of matrix metalloproteinases (MMPs) and VEGF. Additionally, the mature protein forms homodimers and multimers in its native state.
The cDNA for human CD147 was isolated from peripheral blood leukocytes, and was found to be 810 bp in length (Kasinrerk, W. et al., 1992, J. Immunol. 149(3):847-54). The 269 amino acid polypeptide is now known as isoform 2 (Swissprot P35613-2) and is missing residues 24-139 of isoform 1. The 385 amino acid splice variant knows as isoform 1 is expressed only in the retina (Hanna, S. M. et al., 2003, BMC Biochem. 4:17). Other mRNA transcripts, but not proteins, have been reported.
As a protein involved in extracellular matrix remodeling, a process involved in cancer metastasis and wound healing, CD147 is of interest as a therapeutic drug target. For example, Centocor (co-pending application U.S. Ser. No. 61/100,848) and others (Ellis, 1989 Cancer Res 49:3385-91; Biswas et al. Cancer Research 55, 434-439, 1995; Xu, et al. (2007) Hepatology 45: 269-276) have generated neutralizing antibodies against human CD147. The use of a murine an anti-CD147 IgM Mab, CBL1, in human GvHD was reported (Deeg et al. 2001 Blood 98:2052-8).
A need in the art exists to improve current toxicological testing strategies through testing of closely related animal species with human or surrogate biologic proteins. As part of the characterization effort, it is critical to demonstrate reactivity of any therapeutic candidates against the orthologous proteins from available toxicology species, such as baboon.